1. Field of the Invention
The present invention relates to the diagnosis of medical conditions and in particular to medical diagnosis of abnormalities within a female breast which is performed through the use of non-invasive ultrasound techniques to determine whether or not there is any microcalcification in a female breast and further, to determine the location where the microcalcification is located as well as the size of the microcalcification.
2. Description of the Prior Art
In general, breast screening for cancer and microcalcification detection have been performed using different imaging modalities in the prior art and there are several techniques that are currently in active use. The techniques are as follows:
X-Ray Mammography
To date, X-ray mammography is the method of choice and the “gold standard” for breast screening and diagnosis with which other technologies are compared. In order to perform this test a breast is exposed to an X-ray beam whose transmission is measured. The breast is rather strongly compressed between an X-ray sensitive screen and a transparent plate to:                Obtain a uniform thickness,        Reduce the total thickness in order to facilitate operation in the range of lower photon energy levels and higher contrast between tissues, to obtain a clearer image, and        Reduce overlapping of the different inner breast tissues to increase clarity of the image and better sensitivity.        
X-ray mammography was first pioneered by Warren in 1930 but it has been widely used only for the last 30 years. The identification of a breast lesion relies on the imaging of radiographic density changes caused by the lesion and associated changes in breast architecture, vascularity or skin contour. Radiographically, benign lesions are usually less dense than those that are malignant, and in general they have smooth outlines. Malignant lesions, on the other hand, have irregular outlines. When the breast is glandular it is more difficult to image its architecture than when the breast contains large amounts of fat. The breast might be so radiographically dense that breast structure cannot be imaged with sufficient clarity to identify a discrete mass. In the fatty breast the tumor may be clearly visible, as well as changes in vascularity and skin contour. Although, larger tumor in a dense breast can be seen less clearly, it may be identifiable by micro-calcifications. In vivo radiographic studies on the incidence of micro-calcifications show that they can be detected in 40% to 50% of malignant tumors and in about 20% of benign tumors, and histological sections show even higher percentages. Several randomized controlled studies undertaken in different countries to assess the value of screening mammography have demonstrated a clear benefit of screening mammography for women over age 50 or even over the age of 40 in some countries. Although the results for women younger than age 50 are still controversial.
During the last fifteen years, mammography screening has reduced the mortality rate among women with breast cancer considerably1, by detecting approximately 85% to 90% of breast cancers. The reported sensitivity of X-ray mammography varies from 83% to 95%. The reported specificity of X-ray mammography varies from 90% to 98%. However, the reported positive predictive value (PPV) which includes the prevalence of detecting the disease is quite poor, varying from 10% to 50%. 1 “Preventing Chronic Diseases: Investing Wisely in Health Screening to Prevent Cancer Deaths”, U.S. Department of Health and Human Services.
In many developed countries, the film-screen mammography (FSM) is being gradually replaced by full-field digital mammography (FFDM) which is identical to FSM except for the electronic detector that captures and facilitates display of the X-ray signals on a computer or laser-printed film. Although the resolution of the new FFDM instruments is not higher than the traditional FSM technique, additional data processing may help to find tumor marks with higher accuracy.
Two and Three Dimensional Ultrasound Imaging
Conventional ultrasound imaging utilizes megahertz frequency sound waves which reflect at boundaries between tissue with different acoustic impedance, which is the product of the penetrating sound velocity and material density. The time interval of arrival of these reflections is proportional to the depth of field (boundaries of a targeted area). Thus, ultrasound can map acoustic tissue boundaries.
Traditionally, 2-dimensional ultrasound imaging is used as an adjunct to X-ray mammography in the identification and differentiation of cysts or solid masses. Ultrasound imaging of the breast may also help radiologists to evaluate some lumps that can be felt but that are difficult to see on X-ray mammogram, especially in dense breast or implants. It is also in wide use in guided biopsy since it allows real time imaging of the breast. 3-Dimensional ultrasound imaging is seldom used in breast screening due to very limited added information.
Evaluation of the ultrasound technique in distinguishing malignant from benign tumors has shown the accuracy of benign condition detection to be 99.5%. Reportedly, a combination of ultrasonography and standard X-ray mammography has yielded a sensitivity of 92% and a specificity of 98%. With recent advancements in ultrasound platforms, some earlier-stage, clinically occult tumors, that were missed by screening mammography, could be detected. Since the speed of sound in fatty and less fatty breast tissues are approximately the same, ultrasound possesses a promising role in the future screening of younger women with dense breast and high risk factors. However, traditional ultrasound has poor calcification detectability.
Magnetic Resonance Imaging (MRI)
MR images are created by recording the signals generated after radiofrequency excitation of hydrogen nuclei (or other elements) in tissue exposed to a strong static magnetic field. The signals have characteristics that vary according to the tissue type (fat, muscle, fibrotic tissue, etc.).
The method has minimal hazards from magnetic field effects and does not use ionizing radiation. The first MRI results of the human breast were disappointing, but subsequent use of an intravenous gadolinium based contrast agent has offered a clear advance and increased sensitivity. Reportedly, the sensitivity of contrast-enhanced MRI in detection of suspicious breast lesions varies from 88% to 100% (average reported sensitivity of about 95%). However the specificity of the contrast-enhanced MRI has been quoted as rather variable, ranging from 37% to 100%. This is mainly because of considerable exceptions and overlaps in contrast agent uptake and kinetics between benign and malignant tumors. The prevalence of cancer by MRI screening in high risk women is significantly greater than that reported in a similar population screened by ultrasound (4% vs. 1.3%)2. However, neither the technique nor the interpretive criteria are standardized as of to date, leading to variability in performance and in results interpretation. In addition, MRI can only be performed in a setting in which it is possible to perform biopsy of lesions detected solely by MRI. 2 E. A. Morris, L. Liberman, D. J. Ballow et al. 2003 “MRI of Occult Breast Carceonoma in a high risk population”, ARJ 2003; 181:619-626.
Despite its high accuracy in detecting malignancies in breast, MRI is not recommended as a routine examination for the differentiation of benign and malignant lesions/tumors. MRI is a prohibitively expensive modality and it is unsuitable for large-scale screening programs. A US survey conducted by market research firm IVM has revealed that not more than 17% of US imaging facilities provide MRI imaging on site. Nonetheless, where available, MRI can be used as a complementary methodology to assist in differential diagnosis of uncertain lesions.
Positron Emission Tomography (PET) Scan
To conduct a PET scan, a short-lived radioactive tracer isotope, which decays by emitting a positron (chemically incorporated into a metabolically active molecule), is injected into the blood circulation. There is a waiting period while the metabolically active molecule becomes concentrated in tissues of interest; then the patient is placed in the imaging scanner where the positron encounters an electron, producing a pair of photons moving in almost opposite directions. These are detected when they reach a sensitive material in the scanning device, creating a burst of light which is detected by photomultiplier tubes.
Optical Mammography and Spectroscopy of Breast
In the past decade, optical imaging techniques using near-infrared light (NIR) have attracted considerable interest. Characterization, differentiation and localization of different lesions are possible due to the presence of optical absorption contrast between tumors and healthy tissues due to an increased hemoglobin concentration as a result of angiogenesis. The hemoglobin oxygen saturation of suspicious sites can be reconstructed by spectroscopic analysis and can additionally serve as a criterion for diagnosing malignancies. Optical imaging techniques incorporate detection of photons that propagate through the breast with light propagation models to reconstruct the optical properties of the illuminated tissue. By altering the wavelength of the optical source, the spectroscopic dependence of optical properties can be obtained.
An early trans-illumination platform for breast lesion detection demonstrated low sensitivity, specificity and reproducibility. The optical imaging techniques can be split into three groups:    Continuous wave (CW)    Time-domain    Frequency-domain
Each group has its own strengths and weaknesses. Optical imaging techniques have some advantages and drawbacks. The notable advantages are that they:    Are relatively inexpensive    Use NIR and do not impose ionizing radiation    Have potential for portability
The major drawback associated with optical imaging remains light propagation in biological tissue, which is highly scattered, resulting in poor resolution. Improving spatial resolution and discriminating between absorption and scattering remain the biggest challenges that are faced by optical imaging.
Optical mammography has yet to demonstrate its potential to be a stand-alone imaging modality, mainly because of its poor specificity and sensitivity. Nevertheless, it may supplement existing breast imaging techniques by characterizing lesions in suspicious cases, resulting in a reduction of the number of unnecessary biopsies.
Thermo/Photo-Acoustic Breast Imaging
Thermo-acoustics exposes the breast to short pulses of externally applied electromagnetic energy. Differential absorption induces differential heating of the tissue followed by rapid thermal expansion. This generates sound waves that are detected by acoustic transducers positioned around the breast. Tissues that absorb more energy expand more and produce higher amplitude sound waves. The time-of-flight, amplitude and duration of acoustic pulses recorded on the tissue surface possess information regarding the location, absorption and dimensions of the source, thereby permitting a 3-dimensional reconstruction of the targeted absorber.
When the incident electromagnetic energy is visible or NIR light, the term “photo-acoustics” is used instead of thermo-acoustics. Photo-acoustics combines the advantages of two techniques. First, like optical mammography, photo-acoustics probes the optical contrast of the tumor site with respect to surrounding tissue. Secondly, all information about optical absorption inhomogeneities is carried to the breast surface by ultrasound waves which have low attenuation and scattering in soft tissue and thus, resulting in poor sensitivity. Similar to thermo-acoustic techniques, photo-acoustics retain 3-dimensional structural information of the targeted area.
One of the major disadvantages of these techniques is the difficulties in displaying and analyzing the 3-dimensional information retained from the targeted area. Therefore, the time and cost required for image retrieval and analysis of the thermo/photo-acoustic techniques are potentially greater when compared with that of X-ray mammography and ultrasound. Moreover, these techniques have yet to demonstrate reproducibility, adequate sensitivity, specificity and practicality.
A summary of the prior art which will be more understandable after the detailed description of the preferred embodiment is set forth in Table 1 which compares the present invention IDUS technology with leading diagnostic imaging modalities. Also, reference is made to Table 2 at the end of the detailed description of the preferred embodiment which sets forth competing imaging technologies and the strengths and weaknesses of competing imaging technologies as compared with the present invention IDUS system.
There is a significant need for an improved method which will be able to determine not only whether a microcalcification is present in the female breast, but also be able to evaluate the size the location of the microcalcification and through a preset series of information, determine and evaluate whether or not the microcalcification is possibly malignant which would result in further medical treatment and biopsy to remove the microcalcification.